The increasing prevalence of antimicrobial resistance necessitates the development of novel therapeutic agents with improved efficacy and distinct mechanisms of action. In this study, a series of benzimidazole, benzothiazole, and benzoxazole derivatives were evaluated for their antibacterial and antifungal potential using a combined in vitro and in silico approach. The synthesized compounds were screened against Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus, and fungal strains Candida albicans and Aspergillus niger using the agar well dilution method. Several derivatives exhibited significant antimicrobial activity, with benzimidazole-based compounds demonstrating superior potency compared to the other heterocyclic scaffolds. Molecular docking studies were performed to investigate the binding interactions of the synthesized compounds with DNA Gyrase B (PDB ID: 6F86) and Sterol 14-α-demethylase (CYP51, PDB ID: 5V5Z), key targets involved in bacterial DNA replication and fungal ergosterol biosynthesis, respectively. The docking results revealed favorable binding affinities and interaction pro les for the top-ranked compounds, comparable to standard reference drugs Ciprofloxacin and Fluconazole. Structure activity relationship analysis indicated that electron-donating substituents, particularly amino and methoxy groups, enhance antimicrobial efficacy through improved target interactions. Overall, the combined experimental and computational findings highlight benzimidazole derivatives as promising lead candidates for further antimicrobial drug development.

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